To determine the effects of tissue-specific (adipose tissue or muscle) vs global (combined) IR on hepatic triglyceride biosynthesis in humans. To determine differential effects of an acute exercise intervention on hepatic triglyceride biosynthesis…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in %DNL between subjects with global vs muscle-only insulin
resistance as well as the differential effects of premeal exercise on %DNL in
these groups.
Secondary outcome
Associations between plasma markers, metabolites, and increased lipogenesis in
humans with insulin resistance.
Background summary
The promises of precision medicine will be realized with a better understanding
of the heterogeneous physiological phenotypes that underpin common disease
states, such as insulin resistance (IR) and dyslipidemia. We posit that IR is
not a single entity, but the manifestation of discrete tissue-specific
pathologies. For example, we have found that among equally obese patients, some
have global insulin sensitivity, some demonstrate tissue-specific (skeletal
muscle) IR only, and others have global IR. This diversity in IR likely impacts
the pathogenesis of dyslipidemia, thereby explaining some of the variability in
the clinical response to existing lipid-lowering medications (e.g., fibrates).
A better understanding of this heterogeneity may reveal novel therapeutic
targets and help clinicians to provide better precision medicine for patients
with different subtypes of IR.
Study objective
To determine the effects of tissue-specific (adipose tissue or muscle) vs
global (combined) IR on hepatic triglyceride biosynthesis in humans. To
determine differential effects of an acute exercise intervention on hepatic
triglyceride biosynthesis in these groups.
Study design
Observational study with cross-sectional design.
Study burden and risks
Subjects will visit the metabolic unit on 4 occasions (screening, an oral
glucose tolerance test, DNL measurement without and with premeal exercise). A
glucose drink will be used to assess whole-body glucose metabolism and insulin
sensitivity. Stable isotope-labelled water (deuterium) will be used to assess
%DNL into hepatic VLDL. Stable isotopes behave like their natural substrate
(water) and have been previously used without serious adverse effects when
infused or ingested. Overall, the risks associated with participation (pain
from venous blood sampling, nausea from glucose drink) are minimal. We believe
that the scientific value of our study will outweigh the burden and risks
associated with participation.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Ability to give informed consent; - Age 18-65y; - Overweight or class 1
obesity, defined as BMI 25-35 kg/m2; - Modest hypertriglyceridemia, defined as
fasting plasma triglycerides 1.3-3.0mM; - High risk of insulin resistance,
defined as fasting plasma insulin >64pM; - Stable weight for at least 3mo prior
to participation.
Exclusion criteria
- Active or chronic liver disease, kidney disease, congestive heart failure,
unstable angina, history of acute cardiovascular events within 6mo of
screening, history of seizures or syncope, or an active infection requiring
antimicrobial therapy; - Use of insulin, thiazolidinediones, GLP1 agonists,
SGLT2 inhibitors, or sulfonylureas; - Use of fibrates, omega 3 (fish oil),
niacin, or PCSK9 antagonists; - Use of systemic glucocorticoids within 60d
prior to participation; - Hematocrit <35%; - Pregnancy of breastfeeding; -
Active tobacco use, excessive alcohol intake (>14U/wk), or history of drug
abuse.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83166.018.22 |